Objective-There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional imaging data, clinical data, and histopathologic data. Methods and Results-Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high cathepsin-B-related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal, suggesting that molecular imaging yields complimentary new information not available to conventional imaging. Key Words: atherosclerosis Ⅲ cathepsin-B Ⅲ molecular imaging Ⅲ protease Ⅲ structural imaging C onventional imaging approaches such as angiography and ultrasound offer primarily structural information and yields limited data on plaque stability. The degree of carotid stenosis, as determined by structural imaging, is currently the most important therapeutic parameter in deciding on vascular intervention in addition to medical treatment. 1 There is hope that the emerging technologies of molecular imaging could provide a window of insight into the underlying molecular processes that give rise to plaque rupture. [2][3][4] Vulnerable plaques are characterized by the presence of inflammatory mediators and proteolytic enzymes, such as cathepsins and matrix metalloproteinases, which disturb the structural integrity of atheromatous plaques and consequently provoke plaque rupture to expose the lipid-rich plaque interior to thrombin-activating blood cascades. [5][6][7] It is the presence of these molecular species that distinguishes stable atheromatous lesions from unstable ones. We chose to leverage these molecular differences by devising imaging agents to probe for these enzymes. Conclusion-TheseWe and others 2,3,8,9 have developed protease-sensing nearinfrared fluorescent (NIRF) molecular imaging agents that are optically silent at injection because of auto-quenching between closely spaced fluorochromes. After enzyme-specific proteasemediated cleavage, fluorochromes are dequenced and become brightly fluorescent. 2,3,8,9 This technology has potential clinical applicability when combined with an intraoperative NIRF imaging...

A complete surgical resection is the only proven therapeutic modality that prolongs the survival in patients with leiomyosarcoma of the inferior vena cava (IVC). Reconstruction of the IVC is not always necessary but is often required to facilitate venous drainage of the kidney for the tumors at the pararenal area of the IVC. Controversy exists in postoperative adjuvant therapy. Recently, we experienced four cases of pararenal leiomyosarcoma of the IVC, of which treatment consisted of a complete resection of the tumor, ringed polytetrafluoroethylene (PTFE) graft interposition, and bilateral renal vein reconstructions in all patients. Postoperative radiation therapy was instituted in 3 of 4 patients. One patient who did not receive the postoperative radiation therapy was treated with adjuvant chemotherapy. The kidneys were preserved in all patients and no deep vein thrombosis (DVT) or venous insufficiency of the lower extremity veins developed. Distant metastasis to the lung was noted in one patient at 18 months after surgery, who was not received the postoperative radiation therapy but chemotherapy. In conclusion, a complete resection of the tumor, IVC reconstruction, and bilateral renal vein reconstruction followed by adjuvant radiation therapy is recommended for the treatment of pararenal leiomyosarcoma of the IVC.

The collateral flow to the cerebral hemisphere after carotid cross clamping during carotid endarterectomy is mainly through the circle of Willis, and the circle is incomplete in the majority of cases. A correlation between the status of the circle of Willis and the necessity of shunting was evaluated in 67 carotid endarterectomies with pre-operative four-vessel cerebral angiogram. All carotid endarterectomies were performed with selective shunting, based on the change of consciousness and motor function after carotid test clamping under regional anesthesia. Of the 55 patients with either an anterior or a posterior communicating artery, only four (7.3%) required shunting. Twelve patients had neither anterior nor posterior communicating artery, and 10 (83.3%) showed signs of cerebral ischemia necessitating shunting. Mandatory shunt was significantly higher in patients with absence of collaterals (p = 0.00). The rate of intraoperative cerebral ischemia was significantly higher in patients with poor collateral circulation defined by the anatomy of the circle of Willis.